CANINE, BUT NOT RAT BLADDER CONTRACTS TO SEROTONIN VIA ACTIVATION OF 5HT2 RECEPTORS

Serotonin is a biogenic amine that can exert multiple effects on smooth muscle, including smooth muscle of the genitourinary tract; effects that may be species dependent. The present study using isolated tissues documents potent contractile responses to serotonin in canine bladder smooth muscle. Contractile responses to serotonin in canine bladder could be mimicked by α-methyl serotonin, a selective 5HT2 receptor agonist. In fact, although α-methyl serotonin was slightly less potent as a contractile agonist relative to serotonin, the contractile response to α-methyl serotonin was more persistent as evidenced by a greater recovery time to resting force following washout. In contrast, the 5HT(1A) receptor agonist, 8-OH-DPAT and the 5HT3 selective agonist, 2-methyl serotonin, did not markedly contract canine bladder. These data establish that contractile responses to serotonin in the canine bladder are mediated by activation of 5HT2 receptors. We further demonstrated that the 5HT2 receptor antagonist, LY53857, potently inhibited the contractile response to both serotonin and α-methyl serotonin in the canine bladder consistent with agonist activation of 5HT2 receptors. In contrast to the potent response to serotonin observed in the canine bladder, rat bladder preparations did not markedly contract in response to serotonin, α-methyl serotonin, 8-OH-DPAT, or 2-methyl serotonin. Thus, these studies reinforce the marked species variability in responsiveness to serotonin and indicate that contraction to serotonin in the canine bladder is mediated by activation of the 5HT2 receptor.